INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease

This study has been completed.

Sponsor:

Children's Oncology Group

ClinicalTrials.gov Identifier:

NCT01164163

First Posted: July 16, 2010

Last Update Posted: October 23, 2014

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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INCB18424 in Treating Young Patients With Relapsed or Refractory Solid Tumor, Leukemia, or Myeloproliferative Disease

Official Title ICMJE

A Phase I Study of JAK Inhibition (INCB018424) in Children With Relapsed or Refractory Solid Tumors, Leukemias, and Myeloproliferative Neoplasms

Brief Summary

RATIONALE: INCB18424 (Ruxolitinib) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase 1 clinical trial is studying the side effects and best dose of INCB18424 in treating young patients with relapsed or refractory solid tumor, leukemia, or myeloproliferative disease.

To define and describe the toxicities of this treatment administered on this schedule in pediatric patients with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms (MPNs).

To characterize the pharmacokinetics of this treatment in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.

Secondary

To preliminarily define the antitumor activity of this treatment within the confines of a phase I study.

To assess the biologic activity of oral JAK inhibitor INCB18424 upon JAK-STAT signaling in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.

To assess the cytotoxicity and biologic activity of oral JAK inhibitor INCB18424 upon phosphosignaling and mutation burden in pediatric patients whose leukemias or MPNs have known CRLF2 and/or JAK mutations.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral JAK inhibitor INCB18424 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with relapsed or refractory leukemia may receive intrathecal chemotherapy in course 2 and subsequent courses at the discretion of the treating physician.

Plasma, bone marrow, and blood samples may be collected at baseline, during course 1, and before subsequent courses for pharmacokinetic analysis and correlative biology studies.

After completion of study treatment, patients are followed up for 30 days.

Testing for JAK mutations and/or confirmed positive flow cytometry surface staining for the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2); eligibility for part C will be contingent upon patients demonstrating overexpression of CRLF2 by flow cytometric methods measured at either JHU or U. Washington flow laboratories (therefore, pre-enrollment samples need to be sent to one of these laboratories after discussion with Dr. Loh) or if the patient has a CLIA lab documented alteration in JAK1 or JAK2, SH2B3, IL7RA, or another gene that would predict sensitivity to JAK inhibition.

Measurable or evaluable disease (for patients with solid tumors)

Current disease state is one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

ALT ≤ 110 U/L NOTE: *Patients with solid tumors and known bone marrow metastatic disease are eligible for study, but not evaluable for hematologic toxicity. These patients must not be known to be refractory to RBC or platelet transfusions.

Patients with leukemia or MPNs must meet the following criteria:

Platelet count ≥ 20,000/mm^3 (may receive platelet infusions)

Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

ALT ≤ 225 U/L

Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:

≤ 0.6 mg/dL (for patients 1 to < 2 years old)

≤ 0.8 mg/dL (for patients 2 to < 6 years old)

≤ 1 mg/dL (for patients 6 to < 10 years old)

≤ 1.2 mg/dL (for patients 10 to < 13 years old)

≤ 1.4 mg/dL (for female patients ≥ 13 years old)

≤ 1.5 mg/dL (for male patients 13 to < 16 years old)

≤ 1.7 mg/dL (for male patients ≥ 16 years old)

Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal for age

Hydroxyurea may be initiated and continued for up to 24 hours before the start of study treatment

Intrathecal cytarabine (Ara-C) is not myelosuppressive chemotherapy

Patients with leukemia are permitted to receive intrathecal chemotherapy, including methotrexate or cytarabine, only if this is given at the time of diagnostic lumbar puncture at least 24 hours prior to the start of INCB018424